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Conventional electron microscopy (EM) involves dehydration, fixation, and staining of biological samples, which distorts the native state of biological molecules and results in several artifacts. Also, the high-energy electron beam damages the sample and makes it difficult to obtain high-resolution images. These issues can be addressed using cryo-EM, which uses frozen samples and gentler electron beams. The technique was developed by Jacques Dubochet, Joachim Frank, and Richard Henderson, for...
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Related Experiment Video

Updated: Jun 6, 2026

Determination of Molecular Structures of HIV Envelope Glycoproteins using Cryo-Electron Tomography and Automated Sub-tomogram Averaging
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Published on: December 1, 2011

Structural analysis of HIV-1 maturation using cryo-electron tomography.

Alex de Marco1, Barbara Müller, Bärbel Glass

  • 1Structural and Computational Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany.

Plos Pathogens
|December 15, 2010
PubMed
Summary

HIV-1 maturation involves Gag polyprotein cleavage, transforming immature virions into infectious ones. This study reveals structural intermediates during HIV-1 Gag lattice processing, detailing the sequence of changes during maturation.

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Last Updated: Jun 6, 2026

Determination of Molecular Structures of HIV Envelope Glycoproteins using Cryo-Electron Tomography and Automated Sub-tomogram Averaging
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Area of Science:

  • Virology
  • Structural Biology
  • Molecular Biology

Background:

  • Human immunodeficiency virus type 1 (HIV-1) virions mature from an immature, non-infectious state to an infectious form through proteolytic cleavage of the Gag polyprotein.
  • This maturation process involves significant morphological changes, including the formation of a conical core structure within the virion.

Purpose of the Study:

  • To elucidate the sequence of structural changes during HIV-1 maturation by analyzing the Gag lattice structure.
  • To identify structural intermediates associated with ordered Gag polyprotein processing events.

Main Methods:

  • Cryo-electron tomography (cryo-ET) was employed to visualize viral structures.
  • Subtomogram averaging was used to resolve the detailed structure of the Gag lattice in mutant viruses.

Main Results:

  • The study characterized the Gag lattice structure in viruses with mutations affecting Gag cleavage sites.
  • Specific cleavage events, such as between SP1 and NC, were linked to intermediate structural states, potentially maintaining a connection between condensed NC-RNA and the Gag lattice.
  • Disassembly of the immature Gag lattice and assembly of the mature core were found to be dependent on specific cleavage events involving CA-SP1.

Conclusions:

  • The findings provide a detailed structural map of HIV-1 maturation intermediates.
  • The study clarifies the ordered processing events and structural rearrangements of the Gag lattice during HIV-1 virion maturation.